CN100394024C - Micro liquid handling device and methods for using it - Google Patents

Abstract

The invention makes available methods and devices for handling liquids in micro channel systems by means of bubbles generated by a movable light beam. In particular the devices relate to pumps, valves, mixers and thermal reactors in micro channel systems and the combination of these devices into larger systems. The methods relate the preparation and operation of the devices.

Description

Micro liquid handling device and using method thereof

Technical field

The present invention relates to a kind of in the micro passage by by the high energy light source system and method for the vapour bubble treatment fluid that produces of laser for example.The invention still further relates to the various application of this system and method.

Background technique

In nearest 15 years, people are analysis automated more interested and be put to effort for making chemical-biological in the what is called " analysis micro-system ".The for example little TAS of a plurality of overlapping terms (micro-full analytical system), chip lab (Lab-on-a-chip), Biological Chip and living doctor's MEMS (bioMEMS) have been proposed to be used in this technology of description.Although these terms have nothing in common with each other, their purpose all is in order to produce quick and to have cost-benefit chemical-biological analytical system.

The development of these systems faces a lot of challenges, and wherein the most basic challenge is with in good time precisely control mode treatment fluid reagent in micro-system repeatably.As time goes on, occur some kinds of Micropumps and sent scheme.

Wherein a kind of pumping scheme is based on electroosmotic flow/power (EOF), and at first relevant with Capillary Electrophoresis.The EOF phenomenon results from the interaction between the fixed ion point on ion in the solution and the microchannel wall.When the electric field of using along the micro passage, this interaction causes the liquid in the micro passage to be the netted identical electrode of electric charge that flows to its polarity and wall.Under the situation of using silica surface, because the ionization of acidic silanol base makes the electric charge of wall electronegative, and EOF material in negative electrode transports the micro passage.Use the micro-system of EOF pumping for example to describe by people such as Manz.

Though the EOF pump of great use, always is not applicable to basic pumping in the electrophoretic separation system, because they are tending towards influencing the liquid sample that they move and are tending towards being influenced by this liquid sample.Equally, connect outer electrode with liquid in the contact micro passage because the EOF system depends on, this will implement restriction to being applied to single suprabasil EOF number capillaceous.Another shortcoming of EOF pumping is because electrolysis forms bubble.Do not wish that the electric current present path is that bubble in the micro channels liquid is with appreciable impact or actually stop pumping, because electric current may reduce owing to the obstruction of bubble even interrupt.

Another kind of pump is so-called positive displacement pump or membrane pump, actuating wherein cause liquid and thereby liquid stream in pressure reduction.This actuating can be by some devices and light-thermal actuation realizations such as for example piezoelectric element, Pneumatic actuator, magnetic force, electrostatic force.

Light-thermal actuation has illustrated in US 20030021694 (Yevin), wherein utilizes the bubble that is produced by the optical fiber heating liquid by laser to realize the millimicro pumping.Heating location be disperse and finish coupling by manual insertion optical fiber.

Other utilizes the pumping method of light-electric actuation to have illustrated in US 5602386, US 5186001, US5649423 and US 6071081.

US 5602386 relates to a kind of optical drive actuator, wherein, introduce the medium by optical fiber from the light that light source sends, and described light is absorbed in this medium.Thereby the absorption of luminous energy makes the media expansion drive actuator.US 5602386 needs the static positioning and the heavy mechanical valve of light leading device.

US 5186001 relates to a kind of based on the micro-actuator that utilizes the gas in the light source heating sealing chamber, and described wall has the flexible portion that expands and shrink when gas cooling when heated air.The motion of this flexible portion is used for activating.US 5186001 has defective similar to the above, and it comprises the movable partially enclosed chamber that has as reciprocating piston.

US 5649423 relates to a kind of micro linear actuator with capillary force sealing.Light from optical fiber is absorbed in the micro linear actuator, and described absorption makes the liquid evaporation in the actuator.This evaporation increases the pressure in the actuator, and described pressure moves the piston of actuator.US 5649423 comprises the working liquid body that acts on mechanical piston of complete closed.

US 6071081 relates to a kind of micropump, wherein, utilizes laser to pulse and heats air bubble expansion or the contraction that makes that pump chamber is interior.The action of bubble is used as pressure source, and regulates flowing by this pump by the safety check that is positioned at the pump chamber entrance and exit.US 6071081 comprises static state (dispersing) thermal source and mechanical inputs and outlet valve.

People such as Jun have described a kind of miniature assembling type pump, and it utilizes the bubble that passes through row's electric heater formation that moves or expand that liquid is moved by the micro passage.

US 6283718 relates to a kind of micropump based on bubble, this pump comprises a cone-shaped chamber, heats and form vapour bubble near this chamber from metallic heating element or the Ohmic heating that flows through the electric current of the conducting liquid in the narrower micro passage by for example being used to.

US 6513968 relates to a kind of by utilizing discrete thermal source such as light source to produce bubble and by bubble is moved and the method for mixing material in liquid.Motion of air bubbles is mixed liquid.

Generally speaking, pumping scheme of the prior art all has some defectives.Usually they have the use flexibility than low degree, because new analytical applications usually needs new design, and therefore need to produce new Biological Chip, and this is a time-consuming and expensive process.Other assembly that can run into the actuator of disclosed pump and micro-system usually is incompatible problem between detection system, the electrical assembly that is used for for example contacting discrete thermal source and the biological reagent in the micro-system for example.Lacking the space around the micro-system also is a problem, dwindles because the most equipment around the micro-system all are unsuitable for geometric ratio.Micro-system and external control means for engaging are bigger challenges, and are tending towards a large amount of manual operations of needs and are important error source.

At last, the sky high cost valency of each micro-system is to prevent that disposable micro-system from becoming the major obstacle of economically viable modern medical diagnosis and drug screening scheme.

Summary of the invention

The present invention relates to a kind of in micro-system the common solution of treatment fluid, wherein, identical movable light source for example laser is used for for example pumping, regulates one or more processes and thermal cycles such as temperature, mixing, mark, fluorescence excitation.

A purpose of the present invention provides a kind of disposable flexibly micro-system that is used to analyze.

Another object of the present invention provides and a kind ofly need not machinery and/or be electrically connected to the system that is beneficial to little liquid handling and reaction on the drive system.

Another object of the present invention is to obtain a kind of miniature pumping system, and this system has the flexible structure that permission is used for miniature pumping system some application.

Another object of the present invention provides a kind of miniature pumping system, and wherein, pumping light source can be used for handling the liquid in a plurality of micro passages.

The present invention send system to realize above-mentioned and other purpose by the Micropump that produces liquid stream in a kind of described one or more working liquid bodys at least one keeps the micro passage of one or more working liquid bodys, and this system comprises

-keep at least one to comprise that at least one has first section of the first surface part and at least one and has the substrate of second section micro passage of second surface part,

-be suitable for sending the light source of light beam,

-make between light beam and the substrate device that produces relative movement,

This shifter is suitable for will shining between the primary importance of first surface part and the second place that light beam will shine the second surface part at least one light beam and moves, thus the irradiation of each surface portion of response micro passage respectively in first and second sections of micro passage formation at least one act on the vapour bubble of liquid.

According to a second aspect of the invention, realize above-mentioned and other purpose by a kind of method that produces liquid stream at least one micro passage, this method comprises

The substrate that provides at least one to keep at least one micro passage,

Send at least one light beam from least one light source,

-make between described at least one light beam and described at least one substrate to produce relative movement, therefore described at least the first light beam shines the second surface part in primary importance irradiation first surface part and in the second place,

Being radiated at of-response first surface part forms at least one first vapour bubble at least in described the first section,

Being radiated at of-response second surface part forms at least one second vapour bubble at least in described the second section,

Described at least the first and second vapour bubbles act on the liquid in first and second sections of micro passage respectively, flow so that produce in the micro passage.

Described substrate can be any substrate that is suitable for keeping one or more micro passages, for example comprises glass such as fused quartz, silicon, as the substrate of polycarbonate (PC) (PC), polymethylmethacrylate (PMMA) or cycloolefin copolymerization polymer materials such as (COC).

Distance between the relative conduit wall can be chosen between 0.1 μ m (micron)-1mm (millimeter), for example between 0.1 μ m-1 μ m, 1 μ m-10 μ m, 10 μ m-50 μ m, 50 μ m-100 μ m, 100 μ m-200 μ m, 200 μ m-500 μ m or 0.5mm-1mm.

" vapour bubble " refers to the bubble by the liquid formation in the evaporation micro passage.The steam of institute's evaporated liquid can constitute at least 25% of molecule in the vapour bubble, and for example at least 40%, 50%, 60%, 70%, 80%, 90%, 95%, 97.5%, 99% or 99.5%, for example at least 99.9% of described molecule.Preferably, at least 100% of the molecule in the vapour bubble molecule from institute's evaporated liquid.

In a preferred embodiment, vapour bubble expand into is enough to block the liquid stream at place, bubble place by the micro passage cross section.Further preferably, vapour bubble can not move with respect to the position of its formation, unless vapour bubble will be subjected to the guiding of light beam to continue to move in the micro passage.

Liquid can be contained in Micropump and send in one or more parts of system, and for example in one or more micro passages of system, so liquid is substantially enclosed in the passage.

Light beam is can the Continuous irradiation micro passage when primary importance moves to the second place, thereby produces at least one from first section vapour bubble that advances to second section.The working liquid body of micro passage will flow along the direction identical with the light beam movement direction.Thereby, can in the micro passage, realize two-way processing, for example two-way pumping by controlling moving of light beam.

Light beam Continuous irradiation micro passage or its at least one surface portion liquid in can the micro passage is heated to superheat state, thereby forms vapour bubble in the micro passage.By along the continuous mobile beam of passage, formation temperature gradient in formed vapour bubble, and make vapour bubble light beam through later shrink than cool region and/or break and along with light beam be radiated at liquid evaporation and thereby the superheat region that expands expand.The vapour bubble that expands will form pressure pulse and replace liquid volume before pulsing in passage.

The energy density that is radiated at the light beam on the surface portion preferably is chosen to enough height, finishes so that the evaporation of partially liq is instantaneous substantially.Rapid and uniform evaporation will be formed for protecting the not heated protectiveness vapor film of all the other liquid in the channel section.This phenomenon is exactly known " film boiling ".

Alternatively, also can shine the discrete segments of micro passage, the light beam that therefore can respond irradiation first surface part forms at least one first vapour bubble, and the light beam of response irradiation second surface part forms at least one second vapour bubble.Therefore, the sequential illumination of micro passage section forms vapour bubble in proper order.And when the discrete segments of passage is illuminated, guarantee the amphicheirality by the control light beam.Can implement this embodiment to allow described at least the second vapour bubble in the preceding expansion of breaking of described first vapour bubble.Thereby can control the direction that flows that is produced and for example described first vapour bubble be suppressed backflow as current-limiting apparatus.Therefore, for example liquid volume being pumped into another reservoir from for example reservoir equally can be convenient as the obtainable pumping of the Continuous irradiation of utilizing the micro passage.

What it is contemplated that is that configuration disclosed herein can obtain by the continuous or discrete irradiation that utilizes the micro passage equally.

According to another embodiment of the present invention or on the other hand, provide a kind of in the micro passage the miniature pumping system of pumping liquid, this system comprises

-keep at least one to comprise that at least one has first section of the first surface part and at least one and has the substrate of second section micro passage of second surface part;

-be suitable for sending the light source of light beam; With

-be used to device that light beam is moved with respect to substrate,

This shifter is suitable for will shining first surface primary importance and light beam partly at least one light beam and will shines between the second surface second place partly mobile, thereby the irradiation of each surface portion of response micro passage forms at least one respectively and acts on first vapour bubble of liquid and form at least one in second section of micro passage and act on second vapour bubble of liquid in first section of micro passage, wherein, described at least the second vapour bubble formed at least before described the first vapour bubble breaks, so that produce pump action/so that make liquid along moving to described second section direction from described first section.

According to another embodiment of the present invention and on the other hand, provide a kind of in the micro passage method of pumping liquid, this method may further comprise the steps

-provide to keep at least one to comprise that at least one has first section of the first surface part and at least one and has the substrate of second section micro passage of second surface part;

-send light beam from light source; With

-make between light beam and the substrate to produce relative movement, so light beam is in primary importance irradiation first surface part and in second place irradiation second surface part,

Being radiated at of-response first surface part forms at least one first vapour bubble at least in described the first section,

Being radiated at of-response second surface part forms at least one second vapour bubble at least in described the second section,

Wherein, described at least the second vapour bubble formed at least before described the first vapour bubble breaks, so that produce pump action.

Described micro passage can have the one or more zones by the light beam sequential illumination, and each zone all comprises the multistage by light beam order or Continuous irradiation.Therefore, for example can improve the pumping effect by in a passage, having a plurality of continuous each other pumpings zone.

In addition, a zone can be by light beam irradiates repeatedly.Therefore, for example can discharge a plurality of drops from passage, wherein, each drop is discharged in the irradiation that responds each zone.

A zone in the micro passage can along either direction by continuously or sequential illumination repeatedly.Therefore, this system can be two-way, thereby, for example can be at a time point along a direction and produce mobile in opposite direction at another time point.

In addition, imagination can be for example by for being connected to for example computer programming operation that is set by the user the irradiation sequence of each separation region and in special area, will carries out of arbitrary programmable memory device in the described system.

Can in an intended distance, be created in flowing in the micro-system that comprises specific pumping passage, therefore wherein produce the zone of flowing can cover 1 μ m-1cm (centimetre) micro passage length, for example between 1 μ m-10 μ m, 10 μ m-50 μ m, 50 μ m-100 μ m, 100 μ m-200 μ m, 200 μ m-500 μ m, 500 μ m-1mm, 1mm-5mm or 5mm-1cm.In addition, can in an intended distance, be created in flowing in the micro-system that comprises specific pumping passage, therefore wherein produce the length that the zone of flowing can cover at least 1 μ m, for example at least 10 μ m, 25 μ m, 50 μ m, 75 μ m, 100 μ m, 250 μ m, 500 μ m, 1mm, 5mm, 1cm, 5cm or 50cm, for example 100cm at least.

Similarly, the part micro passage that liquid volume wherein will be replaced can have the length of at least 1 μ m, for example at least 10 μ m, 25 μ m, 50 μ m, 75 μ m, 100 μ m, 250 μ m, 500 μ m, 1mm, 5mm, 1cm, 5cm or 50cm, for example 100cm at least.

Can be in conduit wall internal channel wall and passage the intersection of liquid produce heat, perhaps can in passage, directly produce heat the liquid for the transparent conduit wall of the beam optical of sending from light source by providing.

In a preferred embodiment, to the small part substrate be transparent for the wavelength of the light beam that sends from light source.When for example making substrate material, preferably the XIR Extreme Infrared laser of wavelength range from 700nm to 3000nm is used as light source with silicon.When substrate material is for example in visible wavelength region when transparent glass or plastics, use centre wavelength for example to be the red laser diode of 632nm (nanometer), 635nm, 670nm, 680nm or 720nm.

In order to improve luminous energy to heat energy conversion, at least one will comprise a light absorbent that is used to absorb luminous energy by the surface portion of the micro passage of light beam irradiates.This light absorbent can be any be easy to absorb the luminous energy that sends from light source and simultaneously between the light period to the temperature of material insensitive material that raises, aluminium nitride for example, perhaps especially when with silicon when the substrate material doped silicon such as boron-doped silicon or mix phosphorus silicon, perhaps comprise the polymer (the product that for example can buy) of the additive of the absorptivity that improves specific wavelength or a plurality of wavelength from US Clearweld or US Epolin from market.It is enough low to allow a large amount of heats to be sent to the integral part of the conduit wall of passage that this light absorbent can form the thermal resistance of guaranteeing conduit wall.Thereby light absorbent can be used as heating plate with the liquid in the heat tunnel.Light absorbent can absorb the light in the narrower spectral regions, perhaps can be light tight fully and can absorb from ultraviolet to the light of infrared any wavelength.

And substrate can be a light absorbent, and/or light absorbent can be used as substrate.

Light absorbent can be smeared, be sprayed, be deposited or be interspersed on conduit wall, and can form an adjacent layer on conduit wall or be absorbed in the conduit wall.The micro passage of micro-system can be formed by first substrate and second substrate, and described first substrate is transparent for described light beam, and described second substrate has the absorptivity of higher level for described light beam.

Preferably, light absorbent be chosen in light absorbent to absorb the irradiation tunnel wall light beam intensity at least 1%, for example at least 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99%, for example at least 99.99% of the intensity of light beam.

Term " liquid " should broadly explain, and comprises that as non-limiting example uniform liquid, suspension promptly contain the liquid of particulate matter such as particulate or cell, contain the liquid of small bubble, liquid, aqueous, organic liquid, two phase system and hydrophobic liquid and hydrophilic liquid.

In a preferred embodiment, because dissolved gases can be deposited as bubble in the micro passage when the temperature of liquid is elevated to its boiling point,, promptly contain the liquid of minimum dissolved gas so use a kind of de-gas liq.When application was of the present invention, the bubble of deposition may not be hoped.When using moisture liquid in the micro channel systems with hydrophobic channel wall, liquid degassing is even more important, because can sticking on the conduit wall and in time, piles up in bubble.The replacement and/or the means of supplementing out economy of the degassing can be to add scale remover in liquid.

Vapour bubble can be formed in the liquid by nucleation, perhaps can form vapour bubble by making the partially liq film boiling that is delivered to the liquid that is used to form vapour bubble from conduit wall.

The luminous energy of light beam can not have to be absorbed in the liquid under the situation of light absorbent near conduit wall, and perhaps light beam can be absorbed near liquid and the conduit wall the light absorbent simultaneously.If have only liquid will absorb the luminous energy of light beam, the absorptivity of preferably described liquid under the wavelength of described light beam is at least 0.1, for example is 0.5,1,2,3,4,5,6,8,9,10,15,20 at least.Can pass through this absorptivity of standard spectrophotometer measurement.If the absorptivity that records is higher than 1.5, one skilled in the art will know that how liquid diluting is become the diluent liquid absorptivity of acquisition between 0.1 and 1.5 so, and multiply by the absorptivity of dilution factor to obtain to be fit to the absorptivity of diluted sample.

Term " working liquid body " is used for being described in the main liquid of miniature pumping system, for example is any chemistry or biologically active liquid or any liquid that contains particulate matter therefore.

Term " buffering liquid " is used for describing the liquid that is contained in micro channel systems but any chemistry or the biologically active that do not relate in micro channel systems being showed.Buffering liquid may be selected to be and is particularly suitable for selecting especially as vapour bubble formation liquid and/or according to the flowing property of liquid.Preferably, buffering liquid does not mix mutually with working liquid body.

Usually and especially in biosystem, the liquid in the micro passage is worthless so neither also do not heat this liquid by film boiling by nucleation to form vapour bubble to thermal sensitivity.Therefore, in a preferred embodiment of the present invention, make partial buffer liquid film boiling at least or in buffering liquid, form vapour bubble by the response light photograph as mentioned above by the nucleation that responds light beam irradiates.Buffering liquid can be included in the micro passage, is arranged at least to form the zone of vapour bubble.

In another embodiment, be connected for example to form between micro passage and this cavity to small part liquid to be heated-or working liquid body or buffering liquid-can remain in the cavity that links to each other with the micro passage, the surface portion of micro passage is the surface portion of this cavity.Therefore, the surface portion of cavity is by the light beam light photograph, and heat is dissipated in the light absorbent of surface portion or directly is dissipated in the liquid in the cavity.For example, when the working liquid body in the micro passage comprises the suspended matter of the temperature-sensitive cell with predetermined diameter, the size of cavity can be chosen to guarantee that neither one enters cavity in these temperature-sensitive cells, and vapour bubble forms so that act on working fluid in the micro passage simultaneously.Alternatively, the partially liq at least in the cavity can be a buffering liquid.

Therefore cavity can have the opening towards the micro passage, and this opening will be less than being subjected to fire damage to prevent these cells by the cell of the transmission of the working liquid body in the micro passage, and the temperature that for example is exceeded 37 ℃ is destroyed.Alternatively, cavity comprises even can be by the buffering liquid of film and micro passage isolation.

Liquid circulation in the micro-system often can be a laminar flow liquid, similarly, and the mobile normally stratiform that is produced.This laminar flow that can be used for making working liquid body and cushion liquid flows in the micro passage respectively and can not produce mixing substantially.Therefore, can need not in buffering liquid, to form vapour bubble under the situation that special cavity is provided and need not heating work liquid.

In a preferred embodiment, the reynolds' number of liquid stream mostly is 100 most, for example mostly is most 10,5,1,0.5 or 0.01, for example mostly is most 0.001.Reynolds number Re is the ratio of liquid inertia stress and viscous stress, and is defined as $\mathrm{Re}=\frac{v-D}{v}$ , wherein v is the average linear velocity of liquid in the micro passage, D is the diameter or the average cross-section size of micro passage, and v is the liquid kinetic viscosity under the operating temperature.

Another advantage of using buffering liquid is that the characteristic of buffering liquid goes for the special applications of buffering liquid and need not to consider other performance of liquid, for example is used for the suitability of the suspension of specific cells.Therefore, forming the aspect buffering liquids such as absorption of characteristic, surface tension, heat transmitting, specific wavelength at evaporation characteristic for example, vapour bubble can through engineering approaches.

Buffering liquid can be contained in the whole micro-system or at least one section of micro passage can comprise buffering liquid.One section of the micro passage can comprise buffering liquid and working liquid body, and another section can only comprise buffering liquid.For example, the end section of micro passage can comprise buffering liquid.

Advantage with micro passage section that comprises one or more buffering liquids separately is to avoid being close to thermosensitive liquid heating buffering liquid.In a preferred embodiment, one or more micro passage Duan Weiduan sections that comprise buffering liquid, so buffering liquid as piston action in working liquid body.

In micro-system, need be heated to the small part working liquid body usually, especially when using chemistry or biofluid, when reaction with monitored or even when in micro-system, reaching certain temperature and become easy etc.

So according to a further aspect in the invention, micro channel systems comprises

-keep at least one to comprise that at least one has the substrate of first section micro passage of first surface part;

-be suitable for sending the light source of light beam; With

-be used to control the Beam Control device of the parameter of light beam,

Wherein, this Beam Control device is suitable for controlling the parameter of light beam to heat the liquid in the described micro passage.

According to a further aspect in the invention, provide a kind of in the micro passage method of heating liquid, this method comprises

-provide to keep at least one to have the substrate of at least one micro passage of first section;

-send light beam from light source to described at least the first section; With

The parameter of-control light beam

With the liquid in the heating micro passage.

Thereby by carrying out the heating of liquid in the micro passage by the light beam heating liquid.The heat that is dissipated in the liquid depends on a plurality of factors, for example the heat transmitting of the absorption plant of light beam parameters, cavity wall and/or formation part wall, the thermal capacitance of liquid to be heated etc.

Select suitable light beam parameters by details, can in liquid to be heated, obtain predetermined temperature according to liquid and micro-system.As mentioned above, can be for example by reducing the power of light beam and heating liquid with respect to forming the required power of vapour bubble.No matter be, be heated to required energy density of small part liquid and/or pulse width and can be lower than the required a plurality of orders of magnitude of energy density of formation vapour bubble in liquid by nucleation or by film boiling.Evaporation or the required power of heating liquid depend on several parameters, for example the formation of substrate, the liquid in the micro passage and the vapour bubble of the actual size of micro passage, maintenance micro passage and/or the mode of heating.

The energy density of light beam usually can be at 0.001mw (milliwatt)/μ m ²(square micron)-10w (watt)/μ m ²In the scope, for example at 0.001mw/ μ m ²-0.1mw/ μ m ², 0.1mw/ μ m ²-1mw/ μ m ², 1mw/ μ m ²-50mw/ μ m ², 50mw/ μ m ²-250mw/ μ m ², 250mw/ μ m ²-500mw/ μ m ², 0.5w/ μ m ²-1w/ μ m ²Perhaps 1w/ μ m ²-10w/ μ m ²Scope in.The energy density of light beam can be 0.001mw/ μ m at least ², 0.001mw/ μ m at least for example ², 0.01mw/ μ m ², 0.1mw/ μ m ², 1mw/ μ m ², 10mw/ μ m ², 50mw/ μ m ², 100mw/ μ m ², 250mw/ μ m ², 500mw/ μ m ², 1w/ μ m ²Perhaps 5w/ μ m at least ², 10w/ μ m at least for example ²

Imagination can by carry out one group wherein the variable simple experiment of luminous energy density select to be suitable for the luminous energy density of given application, and form and/or mix and/or heating is observed the result that different luminous energy set when taking place and selected luminous energy density at suitable vapour bubble.Visualization device such as light microscope or fluorescence microscope can be used for estimating the result that luminous energy density is set in addition.Fluorescence or colour liquid can be used for making and mix or vapour bubble is shaped visually in addition, and the region of fluid that for example comprises fluorescence liquid mark or contain fluorescent particle can be used for making the result of pumping and/or valve action and/or mixing and/or heating visual.

For by same light source at different time points and/or different components of system as directed heating liquid and/or form vapour bubble, the light source parameters of Beam Control device with control can be provided.Therefore can control light beam parameters for example power, pulse width, energy density and light beam with respect to the speed of micro passage, thereby Beam Control device may command light beam parameters is with the liquid in the heating micro passage.Imagination Beam Control device also can be controlled the parameter of the light beam that is used to form vapour bubble, thereby allows the different designs of for example different micro passage sections.

Therefore energy density, power and/or the pulse width of light beam can be controlled to be enough to in each micro passage section at least partially liq be heated to the temperature of the boiling point that is lower than this liquid thereby in liquid, do not have vapour bubble to form substantially, but also be heated to the temperature that is enough to make for example special reaction or process to take place, for example amplification process such as under the different temperatures that is lower than boiling point at three (about 90-95 ℃ of following sex change/unwind, about 50-65 ℃ anneal down and at last 70-80 ℃ of following polymerization) PCR (PCR) of generation.

For example, liquid to be heated can comprise nucleic acid (NA) amplification mixture that contains primer, nucleic acid, nucleotide monophosphate ester and have the enzyme of polymerase activity.

Can use the technology that is selected from PCR (PCR), strand displacement amplification (SDA), connection-connection-rolling circle amplification (L-RCA) and their combination/change to realize the NA amplification.These methods are known for those skilled in the art, and are for example described by people such as Sambrook.

In addition, the method that realizes nucleic acid (NA) amplification procedure according to the present invention in micro-system may further comprise the steps

A) provide miniature pumping system;

B) provide NA amplification mixture in a section of micro passage, described NA amplification mixture comprises primer, nucleic acid, nucleotide monophosphate ester and has the enzyme of polymerase activity;

C) heat the NA amplification mixture to untie double-stranded DNA with light source;

D) cooling NA amplification mixture so that primer annealing to nucleic acid;

E) enzyme that allows to have polymerase activity extends primer.

Step c)-e) can repeat repeatedly.

In order to monitor the temperature of working liquid body, can use the thermopile element for example infrared detector with the temperature of tracer liquid.In a preferred embodiment, with the thermopile element for example be positioned to from the heating part of liquid send infrared (MIR) light be transferred into the thermopile element by same the physics light path that is used for lead bem, outside just light splitter can be sent to the MIR light that part is transmitted thermopile rather than be sent in the light source.

Make the shifter that produces relative movement between light beam and the substrate can comprise device and/or the device of mobile light source and/or the device of mobile beam of mobile substrate.Substrate can for example be arranged on just like in the optical disk system (Compact Disc like system), wherein, makes substrate in the rotation of light source the place ahead, and this light source can laterally for example moving radially along sense of rotation.

The device of mobile beam comprises the deflection that is used for light beam and/or the device of diffraction, (reflection) mirror for example, prism, grating, hologram etc.

Shifter can be further or is comprised that alternatively for example stepper motor of motor, this stepper motor for example link to each other with reflector to form galvanometer; Perhaps preferably this shifter comprises piezoelectric element, and is used in the fixture motion of deflection and/or diffraction with piezoelectric effect.Alternatively, magnetoelasticity can be used for making described deflection or diffraction component to produce described motion.Alternatively, can use above-mentioned shifter (stepper motor or pressure electric or magnetic bullet element) so that produce relative displacement between light source and the micro-system substrate.

In order to control the light beam of irradiation microchannel surface part, make to produce to relatively move between light beam and the substrate with control and can control the path that light beam passes thereby control gear can be set.

The control gear of control shifter also can comprise the Beam Control device.

In addition, can focuser be set so that light beam focuses at select location.This focuser can be suitable for making light beam to focus on more than in one the plane, thereby is easy to realize driving a plurality of pumping passages in proper order by same light source.

The select location that light beam focuses on can be the surface portion of micro passage, perhaps the position in the micro passage.Focuser can be controlled by focus control device, and preferably suitable for controlling the focus in two or three planes.Therefore, focus can be for example in arbitrary plane the length along passage move heating liquid or vapour bubble is moved along micro passage length for example.

The control gear of control shifter also can comprise focus control device.

Can control the speed of liquid in the micro passage by the energy density of control speed of shifter and/or light source.But, will have preferred, depend on that Micropump for example send the energy density of the special design, micro passage size of system etc.

The generation of vapour bubble can make pressure on the liquid 10 ^-10In the scope of atm (barometric pressure)-50atm, for example 10 ^-10Atm-10 ^-6Atm, 10 ^-6Atm-10 ^-5Atm, 10 ^-5Atm-10 ^-4Atm, 10 ^-4Atm-10 ^-3Atm, 10 ^-2Atm-10 ^-1Atm, 10 ^-1In the scope of atm-1atm, 1atm-5atm, 5atm-10atm, perhaps in the scope of 10atm-50atm.

Send the flow rates of passing through the micro passage cross-section area of generation to be by pump in accordance with the present invention: 0.001pL (picoliter)/min (branch)-100mL (milliliter)/min, 0.001pL/min-0.01pL/min for example, 0.01pL/min-0.1pL/min, 0.1pL/min-1pL/min, 1pL/min-10pL/min, 10pL/min-100pL/min, 1nL (receive liter)/min-10nL/min, 10nL/min-100nL/min, 100nL/min-1 μ L (microlitre)/min, 1 μ L/min-10 μ L/min, 10 μ L/min-100 μ L/min, 100 μ L/min-1mL/min, 1mL/min-10mL/min is perhaps in the scope of 10mL/min-100mL/min.

Also can make the size of vapour bubble be suitable for special system and/or purpose.Therefore the energy density that can be by the control light source and/or the size of control vapour bubble between the light period of select segment.The survival time of vapour bubble can be maximum 10 hours, for example at most per 5 hours, 1 hour, 30 minutes, 10 minutes, 5 minutes, 1 minute, 30 seconds, 10 seconds, 1 second, 0.1 second, 0.01 second, 1 millisecond, 0.1 millisecond, 0.01 millisecond, 1 microsecond or 0.1 microsecond, for example maximum 0.01 microseconds.

For example in order in the micro passage, to obtain valve effect, light source on a particular segment energy density and/or between the light period, for example the pulse width of light beam can be chosen to form its size and the corresponding vapour bubble of micro passage size.Therefore vapour bubble filling channel and thereby in passage, produce current limliting.

In another embodiment of the present invention, set little valve system comprises

-keep at least one to comprise that at least one has first section of the first surface part and at least one and has the substrate of second section micro passage of second surface part;

-be suitable for sending the light source of light beam; With

-be used to device that light beam is moved with respect to substrate,

This shifter is suitable for will shining first surface primary importance and light beam partly at least one light beam and will shines between the second surface second place partly mobile, thereby being radiated to form in the liquid in first section of micro passage and forming at least one second vapour bubble at least one first vapour bubble and the liquid in second section of micro passage of each surface portion of response micro passage, wherein, first and second vapour bubbles are suitable for the formation by making two vapour bubbles or the fluctuation or alternately keep current limliting in the passage of breaking.Preferably, the effect of little valve makes that liquid does not have tomography substantially in the micro passage.

According to another embodiment of the present invention or on the other hand, provide the method for the little valve in a kind of closed micro-system, this method comprises

-provide to keep at least one to comprise that at least one has first section of the first surface part and at least one and has the substrate of second section micro passage of second surface part;

-send light beam from light source; With

-make between light beam and the substrate to produce relative movement, so light beam is in primary importance irradiation first surface part and in second place irradiation second surface part,

Being radiated at of-response first surface part forms at least one first vapour bubble at least in described the first section,

Being radiated at of-response second surface part forms at least one second vapour bubble at least in described the second section,

Wherein, described at least the first and second vapour bubbles are suitable for the formation by making described vapour bubble or the fluctuation or alternately keep current limliting in the passage with closed valve of breaking.

Thereby can in two adjacent micro passage sections for example, form the vapour bubble of two fluctuations, wherein, can control fluctuation so that in described passage, keep at least one vapour bubble restriction.

For example can keep vapour bubble with first and second edge sections that replace the heating steam bubble by shining corresponding micro passage section surface part.

It is preferred that the effect of little valve makes in the micro passage liquid not have tomography substantially.

Preferably, this valve is a kind of normally open valve, comprise by irradiation one or more snippets of micro passage of this valve so that in passage, form the vapour bubble restriction closed this valve.Can break by the vapour bubble that allows to be kept and open this valve.

Can control at least one light source by described shifter flows so that produce in a plurality of micro passages.Can control this shifter to shine a plurality of surface portions of a plurality of micro passages, flow thereby in these a plurality of micro passages, produce liquid.

This at least one light source can be a laser, for example GAS LASERS, solid-state laser, and laser diode for example, perhaps this light source can be light emitting diode (LED), xenon lamp or the incandescent bulb with sufficient intensity.Can utilize mechanical blocking or arrangement for deflecting to regulate xenon lamp or incandescent bulb with pulse mode or continuous-mode operation laser or LED.

In one embodiment of this invention, distance between the adjacent portion of two vapour bubbles in the micro passage is at least 1 micron, for example at least 5 microns, 10 microns, 15 microns, 20 microns, 25 microns, 30 microns, 40 microns, 50 microns, 75 microns, 100 microns, 150 microns, 200 microns, 300 microns, 400 microns, 500 microns, 750 microns, 1000 microns, 1.5 millimeters, 2 millimeters, 3 millimeters, 4 millimeters or 5 millimeters, for example at least 10 millimeters.

In another embodiment of the present invention, distance between the adjacent portion of two vapour bubbles in the micro passage should be maximum 10 millimeters, for example maximum 5 millimeters, 3 millimeters, 1 millimeter, 750 microns, 500 microns, 250 microns, 150 microns, 100 microns, 75 microns, 50 microns, 25 microns, 10 microns or 5 microns, for example maximum 1 micron.

By fluorescence channel or reservoir or stopper navigation system or in order to measure the flow rate of liquid in the micro passage, the special position in can the mark micro-system is normally important with the absolute volume discharge capacity of estimating for example pumping for for example.Therefore, in a preferred embodiment, miniature pumping system can comprise that at least one is used to keep to wait inject the reservoir of the index liquid of described at least one micro passage, with at least one section the attachment hole that is connected described at least one reservoir and described at least one micro passage.Index liquid can for example be fluorescence liquid, colour liquid or the liquid that contains fluorescent particle.Preferred fluorescence liquid has and the essentially identical flow characteristic of working liquid body.

The formation of vapour bubble can also be used for being blended in the multiple liquid that flows in the micro passage, because the mixing in the Micro Channel Architecture almost only relies on the mixing that is caused by diffusion.

According to another embodiment of the present invention or on the other hand, provide a kind of miniature hybrid system of mixing multiple liquid in the micro passage, this system comprises

-keep at least one to comprise that at least one has first section of the first surface part and at least one and has the substrate of second section micro passage of second surface part;

-be suitable for sending the light source of light beam; With

-be used to device that light beam is moved with respect to substrate,

This shifter is suitable for will shining first surface primary importance and light beam partly at least one light beam and will shines between the second surface second place partly mobile, thereby being radiated to form in first liquid in first section of micro passage and forming at least one second vapour bubble at least one first vapour bubble and the liquid in second section of micro passage of each surface portion of response micro passage, thereby increase the border surface area between first and second liquid and therefore increase the mixing that diffusion causes.

According to another embodiment of the present invention or on the other hand, provide a kind of method of mixing at least a first and second liquid in the micro passage, this method comprises

-provide to keep at least one to comprise that at least one has first section of the first surface part and at least one and has the substrate of second section micro passage of second surface part;

-send light beam from light source; With

-make between light beam and the substrate relative movement takes place, so light beam is in primary importance irradiation first surface part and in second place irradiation second surface part,

Being radiated at least a first liquid in described first section of-response first surface part forms at least one first vapour bubble,

Being radiated at least a second liquid in described second section of-response second surface part forms at least one second vapour bubble,

Thereby increase the border surface area between described first and second liquid, with obtain described at least the first and second liquid by for example mixing that causes of diffusion.

In addition, the vapour bubble that is formed in first liquid can be suitable for extending to second liquid from first liquid, and vice versa, thereby further increases the border surface area between first and second liquid.Therefore, on short passage length, realize mixing.Incorporation time can be in the scope of 1 microsecond-10 hour, for example in the scope of 1 microsecond-10 microsecond, 10 microseconds-100 microsecond, 100 microseconds-1 millisecond, 1 millisecond-10 milliseconds, 10 milliseconds-100 milliseconds, 100 milliseconds-1 second, 1 second-30 seconds, 30 seconds-1 minute, 1 minute-10 minutes, 10 minutes-30 minutes, 30 minutes-1 hour, 1 hour-5 hours or 5 hours-10 hours.

In addition, incorporation time can be maximum 10 hours, for example maximum per 5 hours, 1 hour, 30 minutes, 10 minutes, 5 minutes, 1 minute, 30 seconds, 10 seconds, 1 second, 0.1 second, 0.01 second, 1 millisecond, 0.1 millisecond or 0.01 millisecond, and for example maximum 1 microseconds.

The volume of mixing chamber can be at least 10 ^-17Cubic meter, for example at least 10 ^-16Cubic meter, 10 ^-15Cubic meter, 10 ^-14Cubic meter, 10 ^-13Cubic meter, 10 ^-12Cubic meter, 10 ^-11Cubic meter, 10 ^-10Cubic meter, 10 ^-9Cubic meter, 10 ^-8Cubic meter, 10 ^-7Cubic meter, for example at least 10 ^-6Cubic meter.

The volume of mixing chamber can be maximum 10 ^-6Cubic meter, for example maximum 10 ^-7Cubic meter, 10 ^-8Cubic meter, 10 ^-9Cubic meter, 10 ^-10Cubic meter, 10 ^-11Cubic meter, 10 ^-12Cubic meter, 10 ^-13Cubic meter, 10 ^-14Cubic meter, 10 ^-15Cubic meter or 10 ^-16Cubic meter, for example maximum 10 ^-17Cubic meter.

The volume of thermal reactor can be at least 10 ^-17Cubic meter, for example at least 10 ^-16Cubic meter, 10 ^-15Cubic meter, 10 ^-14Cubic meter, 10 ^-13Cubic meter, 10 ^-12Cubic meter, 10 ^-11Cubic meter, 10 ^-10Cubic meter, 10 ^-9Cubic meter, 10 ^-8Cubic meter or 10 ^-7Cubic meter, for example at least 10 ^-6Cubic meter.

The volume of thermal reactor can be maximum 10 ^-6Cubic meter, for example maximum 10 ^-7Cubic meter, 10 ^-8Cubic meter, 10 ^-9Cubic meter, 10 ^-10Cubic meter, 10 ^-11Cubic meter, 10 ^-12Cubic meter, 10 ^-13Cubic meter, 10 ^-14Cubic meter, 10 ^-15Cubic meter or 10 ^-16Cubic meter, for example maximum 10 ^-17Cubic meter.

Imagination can alternately form a plurality of vapour bubbles along the micro passage in first and second liquid to be mixed.Therefore can form the interface that is sinusoidal curve or zigzag first and second liquid substantially, and keep bigger interfacial area, thereby be easy to mix described at least first liquid and second liquid.

Can by control the micro passage described at least the first and second liquid between distance and the controlling and driving hydrostatic pressure.

Can mix in thermal reaction chamber with continuous mode and heat with the constant flow rate by mixing chamber or thermal reactor, perhaps this constant flow rate can be used for intermittent mode, in this intermittent mode, making during mixing in mixing chamber 24 or/and during heating in thermal reactor flows stops.Decide according to practical application during mixing and the adjusting temperature.

It should be understood that any embodiment disclosed herein can make up in many ways so that constitute any possible miniature pumping system.Therefore, can obtain to comprise the miniature pumping system of a plurality of pumping systems, hybrid system and valve system etc., and can comprise by the method for combination in any treatment fluid equally produce to flow, mixing, heating, ventilation etc. and the liquid in the miniature pumping system is carried out any processing.

Description of drawings

Embodiments of the invention are described below with reference to the accompanying drawings, wherein

Fig. 1 illustrates based on the general pumping principle that forms single vapour bubble;

Fig. 2 a-c illustrates the behavioral characteristics based on the general pumping principle that forms single vapour bubble;

Fig. 3 illustrates based on the general pumping principle that forms several vapour bubbles that separate;

Fig. 4 is illustrated in the cross-sectional view that Qi Bishang has the micro passage of light absorbent;

Fig. 5 illustrates the cross-sectional view of the micro passage with the cavity that is used to form vapour bubble;

Fig. 6 a and 6b illustrate the cross-sectional view that wherein vapour bubble is formed on the micro passage in the buffering liquid;

How Fig. 7 can inject the micro passage from reservoir with the buffer solution tagma if illustrating;

Fig. 8 is illustrated in the buffer solution tagma of micro passage and forms vapour bubble;

Fig. 9 illustrates the mechanism of index liquid being injected the liquid of micro passage;

Figure 10 a and 10b illustrate the micro channel systems that is used for mixing two kinds of liquid in mixing chamber;

Figure 11 a illustrates the embodiment of the liquid valve that is formed by vapour bubble, and wherein, two vapour bubbles form in proper order;

Figure 11 b illustrates the embodiment of the liquid valve that is formed by a vapour bubble, and wherein, this vapour bubble is continued to keep;

Figure 12 a and 12b illustrate or utilize the beam spread lens or provide two kinds of patterns of thermal reactor by carry out continuously scanning on whole thermal reactor zone;

Figure 13 illustrates the system of the present invention that comprises mixer and thermal reactor;

Figure 14 a illustrates the system of the present invention of the analytical system that comprises a plurality of-n-independent, and wherein each system all links to each other with the Capillary Electrophoresis passage;

Figure 14 b illustrates the system of the present invention of the analytical system that comprises a plurality of-n-independent, wherein each system all link to each other with the Capillary Electrophoresis passage and all systems all with a shared channel connection;

Figure 15 measures one group of time of the motion diagram of the Laser Driven pump in the motion of being write down;

Figure 16 is the schematic representation that moves among observed Figure 15; With

Figure 17 is the coordinate diagram of the travel distance of bubble in time per unit in the liquid that is illustrated in the micro passage.

Embodiment

Fig. 1 illustrates based on the general pumping principle that forms single vapour bubble.Light source 1 emission light beam 2, this light beam 2 is drawn towards the light absorbent 3 on 4 walls of micro passage.Keeping the substrate of micro passage 4 can be silicon, and light absorbent 3 can be an aluminium nitride.This micro passage 4 is full of the waterborne liquid that has at place's evaporation of light beam heating light absorbent and formation vapour bubble 5.By allowing light beam 2 to move to B from A on light absorbent 3, vapour bubble 5 will move along the direction identical with the movement direction of light beam 2, thereby forces the liquid of micro passage 4 to move along the direction identical with the movement direction of light beam 2.The light beam 2 of light source 1 is by device 6 guiding that are suitable for making light beam to move, and this device 6 is preferably the silicon mirror that is driven and controlled by the computer system (not shown) by piezoelectric actuator.So, can expose to any position of small part micro-system with light beam 2 by computer system.

Fig. 2 a-c illustrates the dynamic process feature based on the general pumping principle that forms single vapour bubble as shown in Figure 1.In Fig. 2 a, light beam heats the wall of micro passage near an A, and forms a local vapour bubble.This vapour bubble is also too little so that can not produce the one-way flow of liquid in the micro passage.In Fig. 2 b, light beam moves along the direction of position B, and vapour bubble has expand into the barrier liquid micro passage of flowing through.Vapour bubble expands along the light beam movement direction, and thereby forces the liquid of micro passage to move in the direction.In Fig. 2 c, light beam is points of proximity B more, and is still forcing liquid to flow along same direction, flowing shown in big arrow among the figure of being produced in the liquid.Along with the wall of micro passage begins to cool down, in the part of the approximated position A of vapour bubble, begin vapor condenses, reduce vapour bubble simultaneously.The contraction of vapour bubble is along the liquid that spurs the vapour bubble left side from A to the direction of B.

Fig. 3 illustrates based on the general pumping principle that forms a plurality of vapour bubbles that separate.This figure is the snapshot that the light beam of light source 1 has shone the longitudinal cross-section figure of the micro passage 4 behind 4 different positions from point A to point B.All be formed with vapour bubble in each position.The vapour bubble 7 in left side is the vapour bubble that forms at first, and has begun to condense and thereby contraction.The liquid in this vapour bubble left side is because contraction is pulled to this vapour bubble.And the adjacent vapour bubble in right side has reached its maximum volume and has blocked the micro passage.Begin several the 3rd vapour bubbles from the left side and still expanding, and just forcing the liquid on its right side to move along the direction from A to B.The 4th vapour bubble 8 just formed, and just begun along the direction from A to B to its right side extruding liquid.New vapour bubble or can be formed on along the micro passage 4 new position for example not between position A and B, perhaps can be formed between position A and the B once more.

Fig. 4 is illustrated in the cross-sectional view of the micro passage 4 that has light absorbent 3 on the one wall.This micro passage 4 be formed on first substrate 9 and the light absorbent 3 that is held in place by second substrate 10 between.Because second substrate 10 is transparent for the wavelength of light beam 2, described light beam will absorb by second substrate, 10 propagation and by the light absorbent 3 that is close to micro passage 4.In the liquid of passage, liquid evaporates under the beam energy of abundance and forms vapour bubble (this vapour bubble is not shown in this Figure) with the energy conduction that forms in the light absorbent 3.

Fig. 5 illustrates the cross-sectional view of the micro-system that is suitable for handling sensitive cells, and described micro-system has the cavity that comprises in the substrate 9 and 10 that is limited to two adjacency or the micro passage 4 of groove 11.The micro passage 4 that comprises groove 11 is full of to have and comprises for example liquid of bio cell 12 of temperature-sensitive particulate matter.Will be destroyed if the cell in the liquid 12 is exposed to above under 37 ℃ the temperature.So by making light beam 2 be radiated on the light absorbent 3 of adjacent trenches 11 and utilizing the liquid evaporation in the groove to form vapour bubble 5 and in cavity or groove, form vapour bubble 5.Groove is designed to enough narrow so that cell 12 is remained on substantially in the wider portion of micro passage cross section.In this embodiment, it is preferred producing vapour bubble 5 by film boiling, because minimum thermal energy conduction should be given the cell 12 in the liquid.

Fig. 6 a illustrates the longitudinal cross-section of the micro passage 4 in the micro-system 13, and wherein vapour bubble 5 is formed in the buffering liquid 14.Buffering liquid 14 and thermosensitive liquid 15 stacked (PARALLEL FLOW), this thermosensitive liquid for example can comprise temperature-sensitive reagent such as antibody, cell or enzyme.Forms vapour bubble 5 by the light absorbent (not shown) illumination beam 2 of substrate 10, thereby form vapour bubble 5 and in most heat energy introducing buffering liquids 14 towards next-door neighbour's buffering liquid 14.Vapour bubble 5 among Fig. 6 a does not also hinder flow of liquid and crosses the micro passage, but when it expand into the size that has corresponding to channel size, it was mobile with barrier liquid.

Fig. 6 b illustrates the alternative of embodiment among Fig. 6 a, and wherein, buffering liquid 14 is introduced into via the inlet 16 that is positioned at left side, vapour bubble formation position, and leaves the micro passage via the outlet 17 that is positioned at vapour bubble formation right side, position.Protected thermosensitive liquid 15 is being continued to flow by direction shown in the big arrow in pump action lower edge that is formed on the vapour bubble in the buffering liquid 14, but the influence that not formed by the vapour bubble in the buffering liquid 14.

Fig. 7 illustrates how the liquid in the reservoir 18 injection micro passages 4 that are full of buffering liquid 14 flow with buffer solution tagma or section 19, and described liquid stream as shown by arrows.Be full of the reservoir 18 that buffering liquid 14 is arranged and be communicated with, and liquid stream is injected in buffer solution tagma 19 by in buffering liquid 14, forming vapour bubble 5 with micro passage 4 fluids.

Fig. 8 is illustrated in the buffer solution tagma 19 that is full of in the micro passage 4 that working liquid body 20 is arranged and forms vapour bubble 5.This buffer solution tagma 19 enters the working liquid body 20 of micro passage 4 from buffering liquid storage device 18 as shown in Figure 7.Given location 19 in the light beam 2 irradiation buffer solution tagmas 19, thus vapour bubble 5 in buffer solution tagma 19, formed.The advantage of this method is that the working liquid body 20 of micro passage can not expose at high temperature.Working liquid bodys 20 can be injected in a plurality of buffer solutions tagma 19, and can be used for the dealing with the work operation of liquid of this buffer solution tagma 19.

Fig. 9 illustrates the mechanism that index liquid 21 is injected working liquid body 20 in the micro passage 4.Be similar to the injection in the described buffer solution of Fig. 7 and Fig. 8 tagma 19, index liquid 21 can be injected working liquid body 20 from the reservoir 18 that is full of underlined liquid 21.Index liquid 21 can be for example to comprise fluorescence molecule or other is easy to the liquid of detected entity.Index liquid 21 can be injected working liquid bodys so that for example make flow velocity in the mobile visual and/or measurement micro passage in the micro passage and/or the leakage situation of test system.By reservoir 18 or with passage that micro passage 4 fluids that hold working liquid body 20 are communicated with in form vapour bubble 5 index liquid 21 injected working liquid bodys 20.By forming vapour bubble 5 to the extinction part 3 of conduit wall, the heat storing wall illumination beam 2 and therefore produce index liquid 21 evaporations that are enough to make the irradiated conduit wall section of next-door neighbour.Alternatively, can form vapour bubble by the index liquid (not shown) that transparent substrates keeps by direct irradiation.When vapour bubble is formed in the marking fluid tagma 22, index liquid will be pushed in the working liquid body 20.Working liquid body stream shown in the arrow will make marking fluid tagma 22 move by micro passage 4.

The channel system 23 that in mixing chamber 24, mixes two kinds of liquid when Figure 10 a and 10b are illustrated in time t=t1 and t=t2.First liquid 25 flows out from first reservoir 27, and second liquid 26 flows out from second reservoir 28.Should flow (shown in arrow) can utilize pump of the present invention and pumping method for example to produce vapour bubbles or by generations such as traditional pumping installations such as reciprocating pump, EOF pump, hydrostatic pressure, capillary flow by the light beam 2 that utilizes light source.First liquid 25 and second liquid 26 are joined, molecule stacked and that form in 29, the first liquid of boundary layer can be diffused in second liquid by this boundary layer, and vice versa.The useful area in boundary layer 29 can 4 confined liquids flow and the vapour bubble 5 of the length in increase boundary layer 29 increases by forming in mixing chamber 24.By changing vapour bubble 5 when the t=t2 mixing efficiency is further improved constantly with respect to t=t1.Preferably in two or more vapour bubbles position-as Figure 10 a position among position and Figure 10 b-between by turns.This can carry out once by turns in per at most 5 minutes, for example maximum per 1 minute, 30 seconds, 10 seconds, 1 second, 0.1 second, 0.01 second or 0.001 second, for example carried out once in per 0.0001 second at most.

Vapour bubble 5 can be formed on the arbitrary position in the mixing chamber 24 usually.In one embodiment of this invention, preferably make vapour bubble 5 be positioned to make the area maximum in the boundary layer 29 in the mixing chamber 24.

Figure 11 a illustrates the embodiment of the liquid valve 30 that is formed by vapour bubble, and two vapour bubbles 31 and 32 orders form, and promptly form one by one.Working liquid body flows through micro passage section 33 along the direction of arrow, and if valve open, this working liquid body also can flow through micro passage section 34,35.Form at least two vapour bubbles adjacent one another are 31 and 32 by order in micro passage section 35 and generate liquid valve.By being used for forming vapour bubbles, thereby make the liquid evaporation of next-door neighbour's microchannel wall from the light beam 2 heating microchannel wall of laser diode 36 (this device that is suitable for light beam is moved is not shown).Light beam 2 is moving corresponding to the position of vapour bubble 31 with between corresponding to the position of vapour bubble 32 with discrete mode.In time series t1, t2 that linearity increases, t3, t4, t5, t6, light beam 2 will add the microchannel wall of thermal proximity vapour bubble 31 when time t1, t3 and t5.When time t2, t4 and t6, light beam 2 will add the microchannel wall of thermal proximity vapour bubble 32.Figure 11 a is the embodiment's of valve a snapshot, and wherein vapour bubble 31 still expand into is enough to block by the flowing of micro passage section 35, but this vapour bubble shrinks.On the other hand, vapour bubble 32 is expanding, and is not enough to block described liquid stream but also expand into.Preferably, the behavioral characteristics of two vapour bubbles is that one of them always blocks flowing by the associated microchannel section.Need not the relevant parameter that undue experimentation those skilled in the art just can determine operating valve, for example the distance between two vapour bubbles and form the in good time behavioral characteristics of vapour bubble.

Figure 11 b illustrates another embodiment of the liquid valve 30 that is formed by single vapour bubble 5, and this vapour bubble 5 is continued to keep.As the alternative of embodiment among Figure 11 a, can be by blocking flowing in the micro passage section 35 by the single vapour bubble that continues to keep from the light beam 2 of laser diode 36 (this device that is suitable for light beam is moved is not shown).Can continue scanning beam 2 by wall and keep vapour bubble 5 along the micro passage 4 that wherein should form and keep vapour bubble.If do not scan the wall of next-door neighbour's vapour bubble 5, but the same position of light beam 2 heated in sequence microchannel wall, and if conduit wall has so absorbed enough energy, vapour bubble will keep fully expanding to block flowing by 4 sections of micro passages.

Figure 12 a and 12b illustrate or utilize beam spread lens 38 or provide two kinds of patterns of thermal reactor 37 by carry out continuously scanning on whole thermal reactor zone.Working liquid body 20 flows to thermal reactor 37 from reservoir 18.In this thermal reactor, for example be used in combination beam spread lens 38 and laser diode 36 (this device that is suitable for light beam is moved is not shown) by laser heating working liquid body 20.Beam spread lens 38 can be the parts of micro-system, and are for example integrated or be installed on this micro-system with micro-system.By using beam spread lens 38, the energy of light beam 2 will be absorbed among the bigger regional 2a, and owing to lower luminous energy density produces lower temperature increase.The working liquid body 20 of major part is moderately heated, and does not cause the local evaporation of the working liquid body 20 in the thermal reactor 37.

Figure 12 b illustrates an embodiment of thermal reactor 37, wherein by scan rapidly on whole thermal reactor 37 with light beam 2 39 and with the energy distribution of light beam 2 on thermal reactor.

In one embodiment of this invention, working liquid body 20 flows through thermal reactor 37 in heating process, so thermal reactor 37 can continuous mode work.In an alternative embodiment, working liquid body 20 is stopped in thermal reactor 37, promptly do not flow through thermal reactor 37, thermal reactor can intermittent mode work like this.Can utilize common valve or valve 30 according to the present invention to make by the mobile of thermal reactor 37 stops.

Because temperature regulation is crucial for obtaining good chemical reaction repeatability, so thermal reactor 37 has multiple application.The thermal cycle of PCR mixture is a kind of very favorable application of thermal reactor.The PCR mixture is pumped in the thermal reactor 37, and can uses thermal reactor 37 by above-mentioned intermittent mode.So-called thermal cycle is carried out in thermal reactor 37.In once circulating, at first the PCR mixture is heated to 90-95 ℃, allow it to be cooled to 55-65 ℃ then, and make temperature rise to 75 ℃ at last.A thermal cycle causes the concentration of selected dna sequence dna to double usually.Thermal cycle repeats 15-30 time usually, and this can similar 1,000,000 times increase the concentration of selected dna sequence dna.

Figure 13 illustrates the system of the present invention that comprises mixer and thermal reactor.Two kinds of working liquid bodys 25 and 26 flow out from reservoir 27,28 respectively.The pump action that can utilize light absorbent 3 to send effect or utilize two light absorbents 40,41 to produce by independent reservoir alternatively by pump in accordance with the present invention produces described liquid stream.Two kinds of working liquid bodys are stacked, thereby form boundary layer 29 between them.Stacked working liquid body flows into mixing chamber 24, and mixes as mentioned above.Mixing material flows into thermal reactor 37, and the laser diode 36 (this device that is suitable for light beam is moved is not shown) and for example beam spread lens 38 that are used as light source heat.Can make the micro-system shown in Figure 13 under constant flow rate with continuous mode work, perhaps can use this micro-system by intermittent mode, in this intermittent mode, making in the mixed process of carrying out in mixing chamber 24 or/and in the heating process of carrying out in thermal reactor 37 flows stops.The time durations that is used to mix and regulates temperature is determined by practical application.

In this embodiment, the light beam from laser diode 36 is used for two kinds of working liquid bodys of pumping 25,26 to mix these liquid and to heat these liquid at thermal reactor 37.In addition, the light beam 2 of laser diode 36 can be used for the molecule in the testing liquid.In fluorscopy, laser diode 36 can be provided for the light beam of fluorescence excitation molecule, and in absorbancy was measured, laser diode 36 can provide the light that will be absorbed in the working liquid body.

Usually, in micro passage, mixing chamber or thermal reactor, can detect.

Figure 13 can be used for carrying out the PCR process of amplifier nucleic acid molecule such as DNA.Reservoir 27 can hold and contain the working liquid body 25 that is useful on the related reagent that carries out the PCR process, and reservoir 28 can hold that contain might maybe may be by the working liquid body 26 of the patient's of pathogenic infection liquid sample.If patient is infected, the DNA of pathogen will be arranged in the liquid sample.Make liquid sample and being used for carry out that the reagent of PCR process is stacked, mixed mixing chamber 24 in to be incorporated in thermal reactor 37 and to carry out thermal cycle.Working liquid body 20 for example can contain the described PH buffer agent of people such as Sambrook and primer to, polymerase, triphosphopyridine nucleotide and salt, and it is known that this primer is of value to the amplification DNA of pathogenic.

Shown in Figure 14 a, several channel systems can be arranged on the same micro-system or in the same micro-system.Have a plurality of-n-independent channel system herein, wherein each channel system all links to each other with Capillary Electrophoresis passage 42 in (the Capillary Electrophoresis passage that only shows channel system 1), and n is an integer.Be similar to Figure 13, channel system comprises mixing chamber 24 and thermal reactor 37.Two kinds of working liquid bodys flowing out from separately reservoir 25 and 26 are stacked and flow into mixing chambers 24.Through behind the mixing chamber 24, they flow into thermal reactor 37, and two mixtures of liquids flow into the loading cross part 43 between CE-passage 42 and the micro passage subsequently.Can utilize Capillary Electrophoresis passage 43 injection and separate small volume mixture in this cross part.For example 44 places carry out fluorscopy in the detection position can to utilize laser diode 36 as excitation source.Actual fluorescence can for example photomultiplier, photodiode, avalanche photodide, ccd video camera (photographic camera) and/or equivalent apparatus be measured by photodetector.The liquid that does not have to separate flows into waste container.

In one embodiment of this invention, mobile the stopping in the part that intersects with CE passage 42 of for example utilizing preferably that the valve of vapour bubble valve of the present invention or other type makes the micro passage.

The combination of mixing chamber 24, thermal reactor 37 and Capillary Electrophoresis (CE) is especially very useful for the PCR process for genetic analysis usually.Can in CE micro passage 42, separate the amplified production of PCR process, and can detect the dna sequence dna that fluorescence PCR products promptly increases in 44 places in the detection position.

Other channel system 1,2......n can be the independent channel systems in the same micro passage.The number of independent channel system can be at least 2 usually, and for example at least 3,4,5,10,15,20,25,30,50,75,100,200,500,1,000,5,000,10,000,20,000 or at least 30,000, at least 50,000 independent channel system for example.

For each micro-system, laser diode 36 can both carry out pumping, mixing, heat treatment and/or valve events (not shown among Figure 14 a) in independent channel system separately.

Figure 14 b illustrates the system of the present invention of the channel system that comprises a plurality of-n-independent, and wherein each system all links to each other with the Capillary Electrophoresis micro passage and all systems all are communicated with a shared micro passage 45.This micro-system is highly suitable for so-called high-effect screening, and in this screening, for example a large amount of drug candidate of screening is so that produce specific reaction with for example acceptor.Reagent working liquid body 25 can comprise the fluorescence labeling acceptor, and multiple sample working liquid body for example 46,47 and 48 can comprise independent medicine so that a kind of working liquid body comprises a kind of drug candidate.Multiple sample working liquid body 46,47 and 48 in mixing chamber separately and reagent working liquid body 25 mix, and can remain in separately the thermal reactor.At last, each reaction product is loaded in the independent CE micro passage, separates this reaction product, and determine to be limited in the amount of the drug candidate on the fluorescence labeling acceptor by fluorscopy.

Also can use a plurality of independent channel systems to make the working liquid body standardization, and analyze with remaining channel system.

Micro-system of the present invention and method can be used for for example high-effect screening or diagnostic analysis, perhaps are used for for example synthesizing of combination of compounds storehouse.

It is variable nucleotide sequence in animals and plants and the microorganism hereditary material and detection of genetic that micro-system of the present invention and method for example can be used for by detecting gene mutation or genetic polymorphism.Genetic polymorphism comprises that the polyphone that is selected from SNP (SNP), variable number repeats the polymorphism of the combination of polymorphism, free flowability repetition DNA, insertion, repetition, disappearance, amplification, rearrangement, SNP, the repetition of short polyphone, two nucleic acid repetitive sequence, gapped repetition DNA and combination thereof.Can be for example by nucleic acid amplification with observe the nucleotides size that many conditions cause or the different variable nucleotide sequences of distinguishing of sequence.

Micro-system of the present invention and method can be used for for example diagnosis of any biologic artifact of any existing biological agents, comprise i) mammalian cell, the cell and the eucaryotic cell that comprise the people, perhaps their part, ii) viral, comprise mammalian virus, human virus and eucaryon virus, perhaps their part, and/or iii) parasitic animal and plant, comprise the mammal parasitic animal and plant, human body parasitic animal and plant and eucaryon parasitic animal and plant, under normal physiological condition, perhaps can be diagnosed as disease, sick epidemic disease, syndrome, under the condition of deficiency disease, perhaps in other potential treating, but under characterization or the diagnosable condition, described cell, virus and/or parasitic animal and plant form the part of human body or animal health.In addition, to can be used for also be not the diagnosis of any other biological agents of a part of prior art for micro-system of the present invention and method.Provide cell, virus and parasitic example below.

Can also be with diagnostic method vector material, for example microbial organisms as saccharomycete and fungi, slime fungi and microorganism, and the microorganism of especially causing a disease.Hereinafter will provide the example of microorganism.And those skilled in the art will know that in this case the reagent that how to make these microorganism target organisms and show the organic feature of described target mates.

Those skilled in the art know how to use or prepare the reagent that is used in particular for any useful target substance usually.Those skilled in the art also will at random obtain common or training medical science and biochemistry textbook and reference manual.

Preferred reagent according to the present invention comprises antigen and/or immune stator, otherwise this stator comprises and is used for contacting with corresponding antigen and antibody and monoclonal antibody that antigen also is in contact with it.When analyzing corresponding to the antibody of special antigen or when screening for example potential deadly virus of human body germ organism or germ microorganism, this may be the problem of being concerned about most.

Diagnostic method according to the present invention can be used for diagnosing serious hybrid type immunodeficiency disease (severecombined immune deficiency), DiGeorge syndrome, MHCI type deficiency disease, MHCII type deficiency disease, prestige Scott-Ao Er Freundlich (Wiskott-Aldrich) syndrome, common variable immunodeficiency, the Agammaglobulinemia disease that X is chain, the chain high immunoglobulinlg M of X (X-linked hyper-IgM) syndrome, selectivity immunoglobulin A (IgA) and/or immunoglobulin M (IgG) deficiency disease, the phagocyte deficiency disease, complement deficiency, NK cell (NK) cell defect, the chain lymphadenia syndrome of X, ataxia telangiectasia, and various from immune lymphadenia disease.Those skilled in the art will know that reagent how to select to diagnose directly or indirectly above-mentioned disease.

According to another method for optimizing provided by the invention, can detect the special cell change and/or the cell differentiation of change.

For example during people's infected person immune deficiency virus (HIV), can mention the change quantity of cd4 cell.Many cells and subcellular fraction incident can be by the specific cells determinants to being expressed by various kinds of cell, or the inspection of T cell differentiation antigen is monitored, these cells comprise the cortex thymocyte, youth's lattice Han Shi (Langerhans) cell, dendritic cell, B cell and their hypotype comprise the B cell in the chronic lymphocytic leukemia, T cell and activated T cell and their precursor, helper cell and inflammatory T cell, cytotoxin T cell, thymocyte, monocyte, leucocyte, lymphocyte, macrophage, the multipotency hematopoietic cell, eosinocyte, basocyte, neutrophil cell, natural killer cell, blood platelet, brain and peripheral nerve cell, vascular smooth muscle cell, enterocyte, smooth muscle cell, blood vessel, marrow stromal cell, bone marrow cell, granulocyte, spinal cord monocyte and brief summary dendritic cell.

Can detect or diagnose the existence of bad pathogenic microorganisms according to another method for optimizing of the present invention, the microorganism that for example belongs to following kind, as Achromobacter xylosoxidans (Achromobacterxylosoxidans), the motionless bacterium of calcium acetate (Acinetobacter calcoaceticus), actinomyces israelii (Actinomyces israelii), have a liking for water monad (Aeromonas hydrophilia), Alcaligenes (Alcaligenes), salmonella arizonae (Arizona hinshawii), anthrax bacillus (Bacillus anthracis), bacillus (Bacillus cereus), bacteroides fragilis (Bacteroides fragilis), bacteroides melaninogenicus (Bacteroides melaninogenicus), Bordetella pertussis (Bordetella Pertussis), borrelia obermeieri (Borreliarecurrentis), Brucella (Brucella), calymmatobacterium granulomatis (Calymmatobacteri μ m granulomatis), embryo's campylobacter intestines subspecies (Campylobacter fetusssp.Intestinalis), embryo's campylobacter jejunum subspecies (CarnPylobacter fetusssp.Jejuni), chlamydiaceae (Chlamydia), chromobacterium violaceum (Chromobacter ri μ mviolace μ m), Citrobacter (Citrobacter), clostridium botulinum (Clostridi μ mbotulin μ m), C.perfringens (Clostridi μ m perfringens), clostridium difficile (Clostridi μ m difficile), clostridium tetani (Clostridi μ m tetani), corynebacterium diphtheriae (Corynebacteri μ m diphteriae), Corynebacterium (Corynebacteri μ m), Bai Shi cock steadite (Coxiella burnetti), blunt tarda (Edwardsiella tarda), erode Aitken bacterium (Eikenella corrodens), Enterobacter (Enterobacter), erysipelothrix rhusiopathiae (Erysipelothrix rhusiopathiae), Escherichia coli (Escherichia coli), flavobacterium meningosepticum (Flavobacteri μ m meningoseptic μ m), soil draws hot francis fungus (Francisella tularensis), Fusobacterium nucleatum (Fusobacteri μ m nucleat μ m), vagina Gardner Salmonella (Gardnerella vaginalis), Ducrey bacillus (Haemopbilusducreyi), Hemophilus influenzae (Haemophilus influenzae), Friedlander (Klebsiella pne μ moniae), Legionella (Legionella), leptospira interrogans (Leptospira interro gans), monocyte Listeria monocytogenes (Listriamonocytogenes), mora Bordetella (Moraxella), Mycobacterium bovis (cobacteri μ mbovis), Mycobacterium leprae (Mycobacteri μ m leprae), Much's bacillus (Mycobacteri μ m tuberculosis), Mycoplasma (Mycoplasma), Diplococcus gonorrhoeae (Neisseria gonorrhoeae), Neisseria meningitidis (Neisseriameningitidis), Nocardia (Nocardia), multocida (Pasteurellamultocida), peptococcus magnus (Peptococcus magnus), Plesiomonas shigelloides (Plesiomonas shigelloides), proteus (Proteus), Providencia (Providencia), pseudomonas aeruginosa (Pseudomonas aeruginosa), pseudomonas mallei (Pseudomonas mallei), Pseudomonas Pseudomallei (Pseudomonaspseudomallei), Dermacentroxenus (Rickettsia), salmonella (Salmonella), Serratia (Serratia), shigella dysenteriae (Shigella dysenteriae), little spirillum (Spirill μ m minor), staphylococcus aureus (Staphylococcus aureus), MRSE (Staphylococcus epidermidis), staphylococcus saprophyticus (Staphylococcussapropbyticus), Streptobacillus moniliformis (Streptobacillus moniliformis), streptococcus (Streptococcus), Streptococcusagalactiae (Streptococcus agalactiae), streptococcus pneumonia (Streptococcus pne μ moniae), streptococcus pyogenes (Streptococcus pyogenes), spot disease treponema (Treponema carate μ m), Spirochaeta pallida (Treponemapallid μ m), superfine treponema (Treponema pertenue), urea mycoplasma (Ureaplasmaurealytic μ m), comma bacillus (Vibrio cholerae), vibrio parahaemolytious (Vibrioparahaemolyticus), yersinia enterocolitica (Yersinia enterocolltica) and Yersinia pestis (Yersinia pestis).

The viral example that exists in can detected sample with micro-system of the present invention and method is an adenovirus, arenavirus, astrovirus, collapse bud virus (Bunyaviruses) (Chinese wall virus), cytomegalovirus, calicivirus, Epstein-Barr virus (Epstein-Barr), the filamentous form virus that comprises Ebola (Ebola) virus, hepatitis A virus, hepatitis B, hepatitis C virus, bleb (Herpes) virus that comprises 1 type and 2 type human herpes simplex vicuses, myxovirus, papillomavirus, papovavirus, parvovirus, picornavirus, togavirus (rubella virus), paramyxovirus and orthomyxovirus, poliovirus, poxvirus, reovirus, rhabdovirus, the retrovirus that comprises human immunodeficiency virus (HIV), Lymphadenopathy-associated virus (LAV), have a liking for T-lymphocyte (H μ man T-lymphotropic) virus (HTLV) with the people, comprise their arbitrary growth HTLV-I, HTLV-II and HTLV-III.

Therefore, can detect any cell that catches that for example causes with system and method for the present invention, virus or parasitic animal and plant, these diseases are the acquired immunity deficiency syndrome for example, actinomycosis, the adenovirus infection anthrax, bacillary dysentery, botulismus, brucellosis, candidiasis, cellulitis, chancroid, cholera, coccidioidomycosis, common cold, conjunctivitis, cystitis, dermatomycosis, diphtheria, endocarditis, bacterial infection (bacterial), epiglottiditis, erysipelas, erysipeloid, enterogastritis, genital herpes, glanders (Glanders), gonorrhoea, hepatitis, reticuloendothelial cytomycosis, impetigo, communicable monokaryon blood cell illness, influenza, legionaires' disease, leprosy, leptospira canicola disease, Lyme arthritis, glander-like disease, leptomeningitis, mumps, nocardiosis, non-gonococcal urethritis, pinta, pestilence, pneumococcal pneumonia, poliomyelitis, primary atypical pneumonia, pseudomembranous enterccolitis, postpartum dense viral disease, rabies, relapsing fever, retrovirus infects, rheumatic fever, American spotted fever (Rocky Mountain spotted fever), rubella, measles, scarlet fever, staphy lococcus infection skin syndrome, the streptococcus pharyngitis, syphilis, tetanus, toxic shock syndrome, toxoplasmosis, tuberculosis, yatobyo, typhoid fever, typhus fever, vaginitis, varicella, breast wart knurl, whooping cough, yaws and yellow fever.

Those skilled in the art will know that how in from the sample of individuality, to test the antibody response of described individuality by inoculating the back, thus the effect of test vaccine.Like this, be easy to test the effect of following vaccine: diphtheria toxoid, tetanus toxoid, pertussis vaccine, poliovirus vaccine, measles vaccine, Mumps Vaccine, nettle rash vaccine, influenza vaccine, tuberculosis vaccines (BacilleCalmetteGu rin or BCG), rabies vacciness, antityphoid vaccine, cholera vaccine and yellow fever vaccine.

Example

In order to check the light driving micro pump desired functional, the structure of executing example of reality of the present invention is as follows:

The SONY laser diode (SLD322V) of 500mW, a 808nm and the current limliting loop that attaches on the computer controlled system are arranged together, and therefore can carry out accurate timing.With focal distance f=8mm, exit aperture is the standard calibration lens calibration laser diode of 5mm; Therefore the diameter of the light beam after the calibration (though because laser diode asymmetric rather than circular) is restricted to 5mm.Light beam after the described calibration is radiated on the dielectric mirror (808nm-Ferroperm Optics, Denmark) that is coated with the Single-handed Dinghy open-Laser metal with miter angle.This mirror is a galvanometric part that is made of 1.8 degree stepper motors with 1: 20 transmission device; This mirror can tilt along either direction with the calibration of 0.09 degree equally.Utilize then the lens of focal distance f=20mm, diameter d=16mm will calibrate and deflection after laser beam focus on the micro-fluid chip.

The mirror of this inclination is positioned at the place apart from polymer chip 50mm, and focusing lens is positioned at the place apart from this chip 20mm simultaneously.By described setting, be enough to obtain 12mm long still focusing and thereby spendable laser beam.

Make computer controlled system in time with stepper motor driving laser together, this motor can send laser at given when and where longshore current body passage in given time period.

Microfluid system is made up of the injection moulding polycarbonate (PC) chip that Switzerland Weidmann Plastics is provided.Channel design is wide by 20-200 μ m rice, recess channels 8 long with 14mm, that 50 μ m are dark and the circular reservoir by 1000 μ m is connected constitutes.On channel design, form this microfluidic circuit by cover piece being installed (utilizing adhesive).This cover piece is made by the glass that is applied with the refractory layer (carrying out the spraying of " thermal spraying " specialty by U.S. PlastiKote) that can resist 815 ℃ of high temperature on thick its of 2mm.Only on a side, apply this refractory layer, and this side is to polymer passage structure-thereby form the four-way wall.Fluid path forms by polymer chip from opposite side by the hole that utilizes 400 μ m, and the reservoir that polymer enters 1000 μ m is run through in this hole.

Utilize injector to inject methyl alcohol to chip, then this chip and aforementioned laser system are put together, so laser beam can penetrate-pass the glass cover piece and is being absorbed the thermosphere that is applied with the selected fluid passage direct connecting place of part respectively from the below.By this microfluidic channel of microscopic examination of the digital camera that has fixing IR-filter is installed.

Test with methyl alcohol; Laser is adjusted to optical output power work with about 300mW, even because under 1 millisecond of pulse width of minimum, it is excessive that obtainable full power 500mW also seems.With galvanometer set for measure 1 second time in the distance of mobile 2mm.Set laser for per 38 milliseconds and send 2 milliseconds of pulses, this equals 5% duty factor, and is actually at the per 100 μ m places that along width are the 2mm passage length of 100 μ m.In case carry out above-mentioned test, just can detect and catch clear and continuous flowing by described vidicon camera.In the process of sending the laser that produces lasting bubble, discharge small collected or dissolved gases.These bubbles with fixed flow rate significantly with on every side liquid by channel flow, thereby proved that when drive system turned back to its starting point or temporarily interrupts, continuous-flow was followed beam direction and stopped suddenly.Further test shows can work reverse pumping by making cycle reverses as described in the specification of the present invention.

The rate of pumping that calculates from the motion diagram of catching is 1500 μ m/s, and thereby the volume flow rate of the correspondence that calculates be 7.5nL/s.

Figure 15 measures one group of time of the motion diagram that write down.5 measure-each at interval 100ms-be illustrated in the air bubble of carrying under one's arms of the 600 μ m that advanced during the 400ms.

Figure 16 is the graphic rendition that utilizes the observed motion of film camera record.5 measure-each at interval 100ms-illustrate the air bubble of carrying under one's arms of the 600 μ m that during 400ms, advanced.

Figure 17 is the coordinate diagram of the travel distance in the expression time per unit.Can drawing always by the diagram point, line illustrates that flow velocity is constant.

Reference

People such as Manz: A.Manz, C.S.Effenhauser, N.Burggraf, D.J.Harrison, K.Seiler, and K.Fluri, " being used to make the electric osmose pumping and the electrophoretic separation of chemical analysis system miniaturization ", J.Micromech, Microeng., vol.4, PP.257-265,1994.

People such as Sambrook: molecular cloning: laboratory manual: the third edition, 1 volume and 2 volumes, people such as Sambrook, 2001, Cold Spring Harbor laboratory publishing house.

People such as Jun: " in the micro passage, utilizing the bubble that passes through to carry out the pumping of small scale ", Thomas K.Jun and Chang-jin Kim.

US20030021694

US5,186,001

US5,602,386

US5,649,423

US6,071,081

US6,283,718

US6,513,968

Claims (32)

1. one kind is used for producing the miniature pumping system that liquid flows in the micro passage of at least one maintenance liquid, and this system comprises

-keep at least one to comprise that at least one has first section of the first surface part and at least one and has the substrate of second section micro passage of second surface part;

-be suitable for sending the light source of light beam; With

-make between light beam and the substrate shifter that produces relative movement,

This shifter is suitable for will shining between the primary importance of first surface part and the second place that light beam will shine the second surface part at least one light beam and moves, thus the irradiation of each surface portion of response micro passage respectively in first and second sections of micro passage formation at least one act on the vapour bubble of liquid.

2. a miniature pumping system as claimed in claim 1 is characterized in that, light beam is in Continuous irradiation micro passage when primary importance moves to the second place, and produces at least one from first section vapour bubble that advances to second section.

3. a miniature pumping system as claimed in claim 1 is characterized in that, the light beam of response irradiation first surface part forms at least one first vapour bubble, and the light beam of response irradiation second surface part forms at least one second vapour bubble.

4. a miniature pumping system as claimed in claim 3 is characterized in that, forms described at least the second vapour bubble at least before described the first vapour bubble breaks.

5. a miniature pumping system as claimed in claim 1 is characterized in that, at least one surface portion of described micro passage comprises the light absorbent that is used to absorb luminous energy.

6. miniature pumping system as claimed in claim 1 also comprises the Beam Control device of the parameter that is used to control light beam.

7. a miniature pumping system as claimed in claim 6 is characterized in that, described Beam Control device is suitable for controlling the parameter of light beam with the liquid in the heating micro passage.

8. a miniature pumping system as claimed in claim 7 is characterized in that, described light beam has is enough to the energy density that near small part liquid is heated to the temperature of the boiling point that is lower than described liquid.

9. a miniature pumping system as claimed in claim 7 is characterized in that, the energy density that is used to heat big quantity of fluid is lower than and is used to energy density that bubble is shaped.

10. a miniature pumping system as claimed in claim 6 is characterized in that, also comprises the thermopile element that is used for the tracer liquid temperature.

11. a miniature pumping system as claimed in claim 1 is characterized in that, the described device that makes light beam comprise mobile substrate with respect to the device of basement movement.

12. a miniature pumping system as claimed in claim 1 is characterized in that, the described device that makes light beam comprise mobile light source with respect to the device of basement movement.

13. a miniature pumping system as claimed in claim 1 is characterized in that, the described device that makes light beam comprise mobile beam with respect to the device of basement movement.

14. a miniature pumping system as claimed in claim 1 also comprises being used to make light beam to focus on the focuser of select location.

15. a miniature pumping system as claimed in claim 14 is characterized in that, select light source energy density and/or light source between the light period to form its size and the corresponding vapour bubble of micro passage size.

16. a miniature pumping system as claimed in claim 15 is characterized in that, forms the vapour bubble of two fluctuations in two adjacent micro passage sections, the control fluctuation is so that keep at least one vapour bubble restriction in described passage.

17. a miniature pumping system as claimed in claim 1 is characterized in that described light source is a laser.

18. miniature pumping system as claimed in claim 1, it is characterized in that, described micro passage comprises at least a first liquid and second liquid to be mixed, wherein, respond being radiated at of at least one first section first surface part and form at least one first vapour bubble at least in described the first liquid, this vapour bubble is suitable for extending in described second liquid, thereby increases the border surface area between first liquid and second liquid.

19. a miniature pumping system as claimed in claim 1, described miniature pumping system also comprises the system that is selected from miniature hybrid system, little valve system and thermal reactor system.

20. a miniature pumping system that is used for pumping liquid in the micro passage, this system comprises

-keep at least one to comprise that at least one has first section of the first surface part and at least one and has the substrate of second section micro passage of second surface part;

-be suitable for sending the light source of light beam; With

-be used to device that light beam is moved with respect to substrate,

This shifter is suitable for will shining first surface primary importance and light beam partly at least one light beam and will shines between the second surface second place partly mobile, thereby the irradiation of each surface portion of response micro passage forms at least one respectively and acts on first vapour bubble of liquid and form at least one in second section of micro passage and act on second vapour bubble of liquid in first section of micro passage, wherein, described at least the second vapour bubble formed at least before described the first vapour bubble breaks, so that produce pump action/so that make liquid along moving to described second section direction from described first section.

21. a method that produces liquid stream at least one micro passage, this method comprises

-the substrate that provides at least one to keep at least one micro passage,

-send at least one light beam from least one light source,

-make between described at least one light beam and described at least one substrate to produce relative movement, therefore described at least the first light beam shines the second surface part in primary importance irradiation first surface part and in the second place,

Being radiated at of-response first surface part forms at least one first vapour bubble at least in described the first section,

Being radiated at of-response second surface part forms at least one second vapour bubble at least in described the second section,

Described at least the first and second vapour bubbles act on the liquid in first and second sections of micro passage respectively, flow so that produce in the micro passage.

22. a method as claimed in claim 21 is characterized in that, thereby comprises when producing at least one from described first section step to described second section mobile vapour bubble from described primary importance Continuous irradiation micro passage when the described second place moves.

23. a method as claimed in claim 22 is characterized in that, the light beam of the described first surface part of response irradiation forms at least one first vapour bubble, and the light beam of the described second surface part of response irradiation forms at least one second vapour bubble.

24. a method as claimed in claim 23 is characterized in that, described at least the second vapour bubble is in the preceding formation of breaking of described at least the first vapour bubble.

25. a method as claimed in claim 20 is characterized in that described system is a two-way working.

26. a method as claimed in claim 20 is characterized in that, at least one surface portion of described micro passage comprises the light absorbent that is used to absorb luminous energy.

27. a method as claimed in claim 25 is characterized in that, luminous energy directly is absorbed in the liquid in the exposure section.

28. a method as claimed in claim 20 is characterized in that, making at least by the response light beam irradiates, the partially liq film boiling forms vapour bubble.

29. a method as claimed in claim 20 also comprises by regulating focuser making light beam focus on select location.

30. a method as claimed in claim 20 is characterized in that, described light source is a laser.

31. the method for a pumping liquid in the micro passage, this method may further comprise the steps

-provide to keep at least one to comprise the substrate that has at least one first section of first surface part and have at least one micro passage of second section of second surface part;

-send light beam from light source; With

-make between light beam and the substrate to produce relative movement, so light beam is in primary importance irradiation first surface part and in second place irradiation second surface part,

Being radiated at of-response first surface part forms at least one first vapour bubble at least in described the first section,

Being radiated at of-response second surface part forms at least one second vapour bubble at least in described the second section,

Wherein, described at least the second vapour bubble formed at least before described the first vapour bubble breaks, so that produce pump action.

32. a method as claimed in claim 31 is characterized in that, obtains described relative movement by mobile substrate, light source and/or light beam.

Images